Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation

Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrP(C)) (porcine PrP [PoPrP]–Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrP(C) susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species. Bioassay proved that PoPrP-Tg001-mice were susceptible only to the classic BSE agent, and PMCA results indicate that only classic BSE can convert pig-PrP(C) into scrapie-type PrP (PrP(Sc)), independently of the species origin. Therefore, conformational flexibility constraints associated with pig-PrP would limit the number of permissible PrP(Sc) conformations compatible with pig-PrP(C), thus suggesting that pig-PrP(C) may constitute a paradigm of low conformational flexibility that could confer high resistance to the diversity of prion strains.